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IntroductionDiet, chronic kidney disease (CKD), and Apolipoprotein L1 (APOL1) (DCA) Study is examining the role of dietary factors in CKD progression and APOL1 nephropathy. We describe enrollment and retention efforts and highlight facilitators and barriers to enrollment and operational challenges, as well as accommodations made in the study protocol.MethodsThe DCA study is enrolling participants in 7 centers in West Africa. Participants who consented were invited to complete dietary recalls and 24-hour urine collections in year 1. We conducted focus groups and semistructured interviews among study personnel to identify facilitators and barriers to enrollment as well as retention and operational challenges in the execution of the study protocol. We analyzed emerging themes using content analyses.ResultsA total of 712 participants were enrolled in 18 months with 1256 24-hour urine and 1260 dietary recalls. Barriers to enrollment were the following: (i) a lack of understanding of research, (ii) the burden of research visits, and (iii) incorporating cultural and traditional nuances when designing research protocols. Factors facilitating enrollment were the following: (i) designing convenient research visits, (ii) building rapport and increased communication between the research team and participants, and (iii) cultural sensitivity - adapting research protocols for the populations involved. Offering home visits, providing free dietary counseling, reducing the volume of study blood collection, and reducing the frequency of visits were some changes made in the study protocol that increased participant satisfaction.ConclusionAdopting a participant-centered approach with accommodations in the protocol for cultural adaptability and incorporating participant feedback is vital for carrying out research in low-income and middle-income regions.

Background During the SARS-CoV-2 global pandemic, one of the longest lockdowns worldwide occurred in Ontario, Canada, during the first wave. For parents and children managing care at home and at risk for COVID-19, the impact on their psychosocial functioning is unknown. Methods A total of 122 families of children aged 2-18 years were enrolled as part of the prospective cohort of childhood nephrotic syndrome and completed a survey during the first wave of the pandemic (August 21-December 10), 2020. In a subset, 107 families had data available pre-pandemic to assess change. Validated measures included the McMaster Family Assessment Device (FAD) for parents and children [greater than or equal to] 12 years for family functioning, the Patient Health Questionnaire for Depression and Anxiety (PHQ-4) for both parent and child, and Pediatric Quality of Life Inventory (PEDSQL[TM]-V4) for children only. Scores were compared using Student's t-test or the Mann-Whitney U test, as appropriate. Results Among the 107 children, 71% were male with a mean age of 9 years old at the time of questionnaire completion, and the mean age of parents was 41 years old. Parents and children reported that family functioning improved during COVID (parent: p < 0.01; child: p = 0.05). Children's overall HRQOL declined (p = 0.04), specifically increased sleep disruption (p = 0.01). Increasing child age was associated with a greater sleep disruption ([beta] = - 1.6 [IQR: - 2.6, - 0.67]) and a related decrease in QOL ([beta] = - 1.0 [IQR: - 1.7, - 0.2]), adjusted for sex. Conclusions Despite the positive effects of family dynamics during the first wave, there were negative effects of sleep disruptions and reduced quality of life in children, especially among older children. Graphical abstract, Author(s): Nowrin F. Aman [sup.1] [sup.2] , Jessica Fitzpatrick [sup.1] [sup.3] , Isabel de Verteuil [sup.1] , Jovanka Vasilevska-Ristovska [sup.1] [sup.2] , Tonny Hue Minh Banh [sup.1] , Daphne J. [...]

Background Idiopathic nephrotic syndrome (INS) is classified in children according to response to initial corticosteroid therapy into steroid-sensitive (SSNS) and steroid-resistant nephrotic syndrome (SRNS), and in adults according to histology into minimal change disease (MCD) and focal segmental glomerulosclerosis (FSGS). However, there is well-recognised phenotypic overlap between these entities. Genome-wide association studies (GWAS) have shown a strong association between SSNS and variation at HLA, suggesting an underlying immunological basis. We sought to determine whether a risk score generated from genetic variants associated with SSNS could be used to gain insight into the pathophysiology of INS presenting in other ways. Methods We developed an SSNS genetic risk score (SSNS-GRS) from the five variants independently associated with childhood SSNS in a previous European GWAS. We quantified SSNS-GRS in independent cohorts of European individuals with childhood SSNS, non-monogenic SRNS, MCD, and FSGS, and contrasted them with SSNS-GRS quantified in individuals with monogenic SRNS, membranous nephropathy (a different immune-mediated disease-causing nephrotic syndrome), and healthy controls. Results The SSNS-GRS was significantly elevated in cohorts with SSNS, non-monogenic SRNS, MCD, and FSGS compared to healthy participants and those with membranous nephropathy. The SSNS-GRS in all cohorts with non-monogenic INS were also significantly elevated compared to those with monogenic SRNS. Conclusions The shared genetic risk factors among patients with different presentations of INS strongly suggests a shared autoimmune pathogenesis when monogenic causes are excluded. Use of the SSNS-GRS, in addition to testing for monogenic causes, may help to classify patients presenting with INS. Graphical abstract, Author(s): Mallory L. Downie [sup.1] [sup.2] , Sanjana Gupta [sup.1] , Melanie M. Y. Chan [sup.1] , Omid Sadeghi-Alavijeh [sup.1] , Jingjing Cao [sup.3] , Rulan S. Parekh [sup.3] [sup.4] [...]

Study objectivesPatients with end-stage kidney disease commonly experience sleep disturbances. Sleep disturbance has been inconsistently associated with mortality risk in patients on hemodialysis, but the burden of symptoms from sleep disturbances has emerged as a marker that may shed light on these discrepancies and guide treatment decisions. This study examines whether functional outcomes of sleep are associated with increased risk of intermediary cardiovascular outcomes or mortality among adults initiating hemodialysis.MethodsIn 228 participants enrolled in the Predictors of Arrhythmic and Cardiovascular Risk in End-Stage Renal Disease study, the Functional Outcomes of Sleep Questionnaire-10 (FOSQ-10), which assesses functional outcomes of daytime sleepiness, was administered within 6 months of enrollment. Intermediary cardiovascular outcomes included QT correction (ms), heart rate variance (ms2), left ventricular mass index (g/m2), and left ventricular hypertrophy. The association of FOSQ-10 score with all-cause mortality was examined using proportional hazards regression.ResultsMean age was 55 years, and median body mass index was 28 kg/m2 (interquartile range, 24, 33), with 70% of patients being African Americans. Median FOSQ-10 score was 19.7 (interquartile range, 17.1, 20.0). A 10% lower FOSQ-10 score was associated with increased mortality risk (hazard ratio, 1.09; 95% confidence interval, 1.01-1.18). Lower FOSQ-10 scores were associated with longer QT correction duration and lower heart rate variance but not left ventricular mass index or left ventricular mass index.ConclusionsIn adults initiating dialysis, sleep-related functional impairment is common and is associated with intermediary cardiovascular disease measures and increased mortality risk. Future studies should assess the impact of screening for sleep disturbances in patients with end-stage kidney disease to identify individuals at increased risk for cardiovascular complications and death.CitationFitzpatrick J, Kerns ES, Kim ED, et al. Functional outcomes of sleep predict cardiovascular intermediary outcomes and all-cause mortality in patients on incident hemodialysis. J Clin Sleep Med. 2021;17(8):1707-1715.

Steroid sensitive nephrotic syndrome is a common condition in pediatric nephrology, and most children have excellent outcomes. Yet, 50% of children will require steroid-sparing agents due to frequently relapsing disease and may suffer consequences from steroid dependence or use of steroid-sparing agents. Several steroid-sparing therapeutic agents are available with few high quality randomized controlled trials to compare efficacy leading to reliance on observational data for clinical guidance. Reported trials focus on short-term outcomes such as time to first relapse, relapse rates up to 1-2 years of follow-up, and few have studied long-term remission. Trial designs often do not consider inter-individual variability, and differing response to treatments may occur due to heterogeneity in pathogenic mechanisms, and genetic and environmental influences. Strategies are proposed to improve the quantity and quality of trials in steroid sensitive nephrotic syndrome with integration of biomarkers, novel trial designs, and standardized outcomes, especially for long-term remission. Collaborative efforts among international trial networks will help move us toward a shared goal of finding a cure for children with nephrotic syndrome., Author(s): Ashlene M. McKay [sup.1] , Rulan S. Parekh [sup.1] [sup.2] [sup.3] [sup.4] [sup.5] , Damien Noone [sup.1] [sup.2] Author Affiliations: (1) grid.42327.30, 0000 0004 0473 9646, Division of Nephrology, [...]

The International Society of Nephrology established the Global Kidney Health Atlas project to define the global capacity for kidney replacement therapy and conservative kidney care, and this second iteration was to describe the availability, accessibility, quality, and affordability of kidney failure (KF) care worldwide. This report presents results for the International Society of Nephrology North America and the Caribbean region. Relative to other regions, the North America and Caribbean region had better infrastructure and funding for health care and more health care workers relative to the population. Various essential medicines were also more available and accessible. There was substantial variation in the prevalence of treated KF in the region, ranging from 137.4 per million population (pmp) in Jamaica to 2196 pmp in the United States. A mix of public and private funding systems cover costs for nondialysis chronic kidney disease care in 60% of countries and for dialysis in 70% of countries. Although the median number of nephrologists is 18.1 (interquartile range, 15.3-29.5) pmp, which is approximately twice the global median of 9.9 (interquartile range, 1.2-22.7) pmp, some countries reported shortages of other health care workers. Dialysis was available in all countries, but peritoneal dialysis was underutilized and unavailable in Barbados, Cayman Islands, and Turks and Caicos. Kidney transplantation was primarily available in Canada and the United States. Economic factors were the major barriers to optimal KF care in the Caribbean countries, and few countries in the region have chronic kidney disease-specific national health care policies. To address regional gaps in KF care delivery, efforts should be directed toward augmenting the workforce, improving the monitoring and reporting of kidney replacement therapy indicators, and implementing noncommunicable disease and chronic kidney disease-specific policies in all countries.

BackgroundA better understanding of the pathophysiology involving coronary artery calcification (CAC) in patients on hemodialysis (HD) will help to develop new therapies. We sought to identify the differences in metabolomics profiles between patients on HD with and without CAC.MethodsIn this case-control study, nested within a cohort of 568 incident patients on HD, the cases were patients without diabetes with a CAC score >100 (n=51), and controls were patients without diabetes with a CAC score of zero (n=48). We measured 452 serum metabolites in each participant. Metabolites and pathway scores were compared using Mann-Whitney U tests, partial least squares-discriminant analyses, and pathway enrichment analyses.ResultsCompared with controls, cases were older (64±13 versus 42±12 years) and were less likely to be Black (51% versus 94%). We identified three metabolites in bile-acid synthesis (chenodeoxycholic, deoxycholic, and glycolithocholic acids) and one pathway (arginine/proline metabolism). After adjusting for demographics, higher levels of chenodeoxycholic, deoxycholic, and glycolithocholic acids were associated with higher odds of having CAC; comparing the third with the first tertile of each bile acid, the OR was 6.34 (95% CI, 1.12 to 36.06), 6.73 (95% CI, 1.20 to 37.82), and 8.53 (95% CI, 1.50 to 48.49), respectively. These associations were no longer significant after further adjustment for coronary artery disease and medication use. Per 1 unit higher in the first principal component score, arginine/proline metabolism was associated with CAC after adjusting for demographics (OR, 1.83; 95% CI, 1.06 to 3.15), and the association remained significant with additional adjustments for statin use (OR, 1.84; 95% CI, 1.04 to 3.27).ConclusionsAmong patients on HD without diabetes mellitus, chenodeoxycholic, deoxycholic, and glycolithocholic acids may be potential biomarkers for CAC, and arginine/proline metabolism is a plausible mechanism to study for CAC. These findings need to be confirmed in future studies.

BackgroundEnd-stage kidney disease (ESKD) is a significant public health concern disproportionately affecting African Americans (AAs). Type 2 diabetes (T2D) is the leading cause of ESKD in the USA, and efforts to uncover genetic susceptibility to diabetic kidney disease (DKD) have had limited success. A prior genome-wide association study (GWAS) in AAs with T2D-ESKD was expanded with additional AA cases and controls and genotypes imputed to the higher density 1000 Genomes reference panel. The discovery analysis included 3432 T2D-ESKD cases and 6977 non-diabetic non-nephropathy controls (N = 10,409), followed by a discrimination analysis in 2756 T2D non-nephropathy controls to exclude T2D-associated variants.ResultsSix independent variants located in or near RND3/RBM43, SLITRK3, ENPP7, GNG7, and APOL1 achieved genome-wide significant association (P

IntroductionMagnesium (Mg) may protect against arterial calcification. We tested the hypotheses that a higher serum Mg concentration is associated with less arterial calcification and stiffness in patients on hemodialysis (HD) and that these associations are modified by diabetes mellitus.MethodsWe performed cross-sectional analyses of 367 incident HD patients from the Predictors of Arrhythmic and Cardiovascular Risk in End Stage Renal Disease (PACE) cohort. Measures of arterial calcification and stiffness included coronary arterial calcification (CAC) and thoracic aortic calcification (TAC) scores, ankle brachial index (ABI; high ABI: >1.4 or incompressible vessels), pulse wave velocity (PWV), and pulse pressure.ResultsMean Mg was 1.8 ± 0.2 mEq/l and 58% had diabetes. Among nondiabetic individuals, per 0.1 mEq/l higher Mg, non-zero CAC score was lower (% difference: -15.4%; 95% confidence interval [CI]: -28% to -0.55%; P = 0.03), the odds of having TAC score >0 and the odds of having high ABI were lower (odds ratio [OR]: 0.66; 95% CI 0.47-0.93; P = 0.02, and 0.23; 95% CI: 0.06-0.83, P = 0.03, respectively) while adjusting for demographics, comorbidities, markers of mineral metabolism, and dialysis clearance. Among diabetic individuals, per 0.1 mEq/l higher Mg, the odds of having TAC score >0 was higher (OR: 1.57; 95% CI: 1.09-2.26; P = 0.02). Mg was not associated with CAC or high ABI among diabetic individuals. Mg was not associated with PWV or pulse pressure regardless of diabetes status.ConclusionDiabetes modified the associations of serum Mg with arterial calcification and stiffness in incident HD patients. Higher Mg was associated with less arterial calcification and less peripheral arterial stiffness among nondiabetic individuals, but Mg was only associated with TAC among diabetic individuals with higher Mg being associated with higher likelihood of having TAC score >0.

BackgroundFrail obese community-dwelling older adults are at increased mortality risk. Among hemodialysis (HD) patients, frailty is common and associated with increased mortality risk; however, in dialysis, obesity is associated with decreased mortality risk. Whether the frail-obese phenotype is associated with increased mortality risk among HD patients remains unclear.MethodsThis study included 370 incident HD patients enrolled in the Predictors of Arrhythmic and Cardiovascular Risk in End Stage Renal Disease (PACE) study. We measured frailty using the Fried phenotype, general obesity [body mass index (BMI) ≥30 kg/m2] and abdominal obesity [waist:hip ratio (WHR) ≥median WHR] and estimated their associations with mortality.ResultsThe mean age was 55 years, with 42% female, 73% African American, 57% diabetic and 52% frail. Frail HD patients had higher mean BMI (frail = 30.3 kg/m2, non-frail = 28.3 kg/m2; P = 0.02) and similar WHR (P = 0.8). Twenty-two percent were frail with general obesity and 27% were frail with abdominal obesity. Frailty was associated with 1.66-fold increased mortality risk [95% confidence interval (CI) 1.03-2.67]. BMI was associated with a decreased mortality risk [25.0-29.9 kg/m2 hazard ratio (HR) 0.53 (95% CI 0.31-0.93); ≥30 kg/m2 HR 0.34 (95% CI 0.19-0.62)]. Frailty was associated with elevated mortality risk among HD patients with general [HR 3.77 (95% CI 1.10-12.92)] and abdominal obesity [HR 2.38 (95% CI 1.17-4.82)]. Frailty was not associated with mortality among HD patients without general or abdominal obesity.ConclusionsIn adults initiating HD, frailty was associated with elevated mortality risk, even among the obese. Frail-obese HD patients may be a high-risk, often-overlooked population, as obesity is assumed to be protective. Measurement of frailty and obesity may facilitate risk stratification.

ObjectiveTo better define the prevalence of protein-energy wasting (PEW) in kidney disease is poorly defined.MethodsWe performed a meta-analysis of PEW prevalence from contemporary studies including more than 50 subjects with kidney disease, published during 2000-2014 and reporting on PEW prevalence by subjective global assessment or malnutrition-inflammation score. Data were reviewed throughout different strata: (1) acute kidney injury (AKI), (2) pediatric chronic kidney disease (CKD), (3) nondialyzed CKD 3-5, (4) maintenance dialysis, and (5) subjects undergoing kidney transplantation (Tx). Sample size, period of publication, reporting quality, methods, dialysis technique, country, geographical region, and gross national income were a priori considered factors influencing between-study variability.ResultsTwo studies including 189 AKI patients reported a PEW prevalence of 60% and 82%. Five studies including 1776 patients with CKD stages 3-5 reported PEW prevalence ranging from 11% to 54%. Finally, 90 studies from 34 countries including 16,434 patients on maintenance dialysis were identified. The 25th-75th percentiles range in PEW prevalence among dialysis studies was 28-54%. Large variation in PEW prevalence across studies remained even when accounting for moderators. Mixed-effects meta-regression identified geographical region as the only significant moderator explaining 23% of the observed data heterogeneity. Finally, two studies including 1067 Tx patients reported a PEW prevalence of 28% and 52%, and no studies recruiting pediatric CKD patients were identified.ConclusionBy providing evidence-based ranges of PEW prevalence, we conclude that PEW is a common phenomenon across the spectrum of AKI and CKD. This, together with the well-documented impact of PEW on patient outcomes, justifies the need for increased medical attention.

BACKGROUND:Mortality in end-stage renal disease (ESRD) occurs predominantly from cardiovascular disease (CVD) and sudden cardiac death (SCD). Obstructive sleep apnea (OSA) is characterized by periodic airflow limitation associated with sleep arousal and oxygen desaturation and is prevalent in patients with ESRD. Whether OSA increases the risk for SCD, cardiovascular and all-cause mortality among hemodialysis patients remains unknown. METHODS:In a prospective cohort of 558 incident hemodialysis patients, we examined the association of OSA with all-cause mortality, cardiovascular mortality, and SCD using Cox proportional hazards models controlling for traditional CVD risk factors. RESULTS:Sixty-six incident hemodialysis patients (12%) had OSA. Mean age (56 years) and percentage of males (56%) were identical in OSA and no-OSA groups. Fewer African Americans had OSA than non-African Americans (9 vs. 18%, respectively). Participants with OSA had higher body-mass index, Charlson comorbidity score, and left ventricular mass index and greater prevalence of diabetes and coronary artery disease. During 1,080 person-years of follow-up, 104 deaths occurred, 29% of which were cardiovascular. OSA was associated with a higher risk of all-cause mortality (HR 1.90 [95% CI 1.04-3.46]) and cardiovascular mortality (HR 3.62 [95% CI 1.36-9.66]) after adjusting for demographics and body-mass index. OSA was associated with a higher risk of SCD after adjusting for demographics (HR 3.28 [95% CI 1.12-9.57]) and multiple cardiovascular risk factors. CONCLUSIONS:Incident hemodialysis patients with OSA are at increased risk of all-cause and cardiovascular mortality and SCD. Future studies should assess the impact of screening for OSA and OSA-targeted interventions on mortality in ESRD.

BackgroundThe risk of cardiovascular mortality is high among adults with end-stage renal disease (ESRD) undergoing hemodialysis. Waist-to-hip ratio (WHR), a metric of abdominal adiposity, is a predictor of cardiovascular disease (CVD) and mortality in the general population; however, no studies have examined the association with CVD mortality, particularly sudden cardiac death (SCD), in incident hemodialysis.MethodsAmong 379 participants incident (< 6 months) to hemodialysis enrolled in the Predictors of Arrhythmic and Cardiovascular Risk in ESRD study, we evaluated associations between WHR and risk of CVD mortality, SCD, and non-CVD mortality in Cox proportional hazards regression models.ResultsAt study enrollment, mean age was 55 years with 41% females, 73% African Americans, and 57% diabetics. Mean body mass index was 29.3 kg/m2, and mean WHR was 0.95. During a median follow-up time of 2.5 years, there were 35 CVD deaths, 15 SCDs, and 48 non-CVD deaths. Every 0.1 increase in WHR was associated with higher risk (hazard ratio [95% CI]) of CVD mortality (1.75 [1.06-2.86]) and SCD (2.45 [1.20-5.02]), but not non-CVD mortality (0.93 [0.59-1.45]), independently of demographics, body mass index, comorbidities, inflammation, and traditional CVD risk factors.ConclusionsWHR is significantly associated with CVD mortality including SCD, independently of other CVD risk factors in incident hemodialysis. This simple, easily obtained bedside metric may be useful in dialysis patients for CVD risk stratification.

BackgroundSudden cardiac death (SCD) is the most common etiology of death in hemodialysis patients but not much is known about its risk factors. The goal of our study was to determine the association and risk prediction of SCD by serum N-terminal prohormone of brain natriuretic peptide (NTproBNP) troponin I (cTnI) in hemodialysis patients.MethodsWe measured NTproBNP and cTnI in 503 hemodialysis patients of a national prospective cohort study. We determined their association with SCD using Cox regression, adjusting for demographics, co-morbidities, and clinical factors and risk prediction using C-statistic and Net Reclassification Improvement (NRI).ResultsPatients' mean age was 58 years and 54 % were male. During follow-up (median 3.5 years), there were 75 outpatient SCD events. In unadjusted and fully-adjusted models, NTproBNP had a significant association with the risk of SCD. Analyzed as a continuous variable, the risk of SCD increased 27 % with each 2-fold increase in NTproBNP (HR, 1.27 per doubling; 95 % CI, 1.13-1.43; p 7,350 pg/mL) compared with the lowest tertile (

BackgroundThe presence of population structure in a sample may confound the search for important genetic loci associated with disease. Our four samples in the Family Investigation of Nephropathy and Diabetes (FIND), European Americans, Mexican Americans, African Americans, and American Indians are part of a genome- wide association study in which population structure might be particularly important. We therefore decided to study in detail one component of this, individual genetic ancestry (IGA). From SNPs present on the Affymetrix 6.0 Human SNP array, we identified 3 sets of ancestry informative markers (AIMs), each maximized for the information in one the three contrasts among ancestral populations: Europeans (HAPMAP, CEU), Africans (HAPMAP, YRI and LWK), and Native Americans (full heritage Pima Indians). We estimate IGA and present an algorithm for their standard errors, compare IGA to principal components, emphasize the importance of balancing information in the ancestry informative markers (AIMs), and test the association of IGA with diabetic nephropathy in the combined sample.ResultsA fixed parental allele maximum likelihood algorithm was applied to the FIND to estimate IGA in four samples: 869 American Indians; 1385 African Americans; 1451 Mexican Americans; and 826 European Americans. When the information in the AIMs is unbalanced, the estimates are incorrect with large error. Individual genetic admixture is highly correlated with principle components for capturing population structure. It takes ~700 SNPs to reduce the average standard error of individual admixture below 0.01. When the samples are combined, the resulting population structure creates associations between IGA and diabetic nephropathy.ConclusionsThe identified set of AIMs, which include American Indian parental allele frequencies, may be particularly useful for estimating genetic admixture in populations from the Americas. Failure to balance information in maximum likelihood, poly-ancestry models creates biased estimates of individual admixture with large error. This also occurs when estimating IGA using the Bayesian clustering method as implemented in the program STRUCTURE. Odds ratios for the associations of IGA with disease are consistent with what is known about the incidence and prevalence of diabetic nephropathy in these populations.

Background Steroids and/or steroid-sparing medications are commonly used for nephrotic syndrome treatment; however, the impact of these medications on health-related quality of life over time is not well described. Methods Longitudinal cohort is up to 5 years where children were assessed with baseline and annual Pediatric Quality of Life Inventory questionnaire. A mixed-effects linear regression determined differences in scores among children receiving steroids and/or steroid-sparing agents for at least 30 days compared with those not on medication at 1, 3, 6, and 12 months prior to assessment. Results Among 295 children, 64% were male, with a median age of 3.7 (interquartile range [IQR], 2.7, 5.9) years at diagnosis, and comprised 25% Europeans, 40% South Asians, and 8% East/Southeast Asians. Adjusted HRQOL scores were reduced among children taking steroids and steroid-sparing agents among 705 HRQOL measures (median 2 [IQR, 1, 3] per child). Compared to children without medication, steroid and steroid-sparing agent use up to 12 months prior to assessment were associated with an overall HRQOL drop of 3.17 (95% confidence interval [CI], - 5.25, - 1.08) and 3.18 (95% CI, - 5.24, - 1.12), respectively, after adjustment. Functioning domain scores were reduced by 4.41 points (95% CI, - 6.57, - 2.25) in children on steroids, whereas fatigue domain scores were reduced by 5.47 points (95% CI, - 9.28, - 1.67) in children on steroid-sparing agents after adjustment. Conclusions HRQOL is consistently decreased in children receiving steroids and steroid-sparing agents, with differential effects on functioning and fatigue. Counseling families on possible effects of prolonged treatment periods is important in the management of childhood nephrotic syndrome., Author(s): Shawn Khullar [sup.1] [sup.2] , Tonny Banh [sup.1] , Jovanka Vasilevska-Ristovska [sup.1] , Rahul Chanchlani [sup.3] [sup.4] , Josefina Brooke [sup.5] , Christoph P. B. Licht [sup.5] [sup.6] [sup.7] [...]

Diabetic kidney disease (DKD) is the most common etiology of chronic kidney disease (CKD) in the industrialized world and accounts for much of the excess mortality in patients with diabetes mellitus. Approximately 45% of U.S. patients with incident end-stage kidney disease (ESKD) have DKD. Independent of glycemic control, DKD aggregates in families and has higher incidence rates in African, Mexican, and American Indian ancestral groups relative to European populations. The Family Investigation of Nephropathy and Diabetes (FIND) performed a genome-wide association study (GWAS) contrasting 6,197 unrelated individuals with advanced DKD with healthy and diabetic individuals lacking nephropathy of European American, African American, Mexican American, or American Indian ancestry. A large-scale replication and trans-ethnic meta-analysis included 7,539 additional European American, African American and American Indian DKD cases and non-nephropathy controls. Within ethnic group meta-analysis of discovery GWAS and replication set results identified genome-wide significant evidence for association between DKD and rs12523822 on chromosome 6q25.2 in American Indians (P = 5.74x10-9). The strongest signal of association in the trans-ethnic meta-analysis was with a SNP in strong linkage disequilibrium with rs12523822 (rs955333; P = 1.31x10-8), with directionally consistent results across ethnic groups. These 6q25.2 SNPs are located between the SCAF8 and CNKSR3 genes, a region with DKD relevant changes in gene expression and an eQTL with IPCEF1, a gene co-translated with CNKSR3. Several other SNPs demonstrated suggestive evidence of association with DKD, within and across populations. These data identify a novel DKD susceptibility locus with consistent directions of effect across diverse ancestral groups and provide insight into the genetic architecture of DKD.

BackgroundAPOL1 genotype is associated with advanced kidney disease in African Americans, but the pathogenic mechanisms are unclear. Here, associations of APOL1 genotype with urine biomarkers of glomerular and tubular injury and kidney function decline were evaluated.Study designObservational study.Setting & participants431 human immunodeficiency virus (HIV)-infected African American women enrolled in Women's Interagency HIV Study (WIHS).PredictorAPOL1 genotype.OutcomesAlbumin-creatinine ratio (ACR), 4 tubular injury biomarkers (interleukin 18 [IL-18], kidney injury molecule 1 [KIM-1], neutrophil gelatinase-associated lipocalin [NGAL], and α1-microglobulin [A1M]), and kidney function estimated using the CKD-EPI cystatin C equation.MeasurementsParticipants were genotyped for APOL1 single-nucleotide polymorphisms rs73885319 (G1 allele) and rs71785313 (G2 allele). Urine biomarkers were measured using stored samples from 1999-2000. Cystatin C was measured using serum collected at baseline and 4- and 8-year follow-ups.ResultsAt baseline, ACRs were higher among 47 women with 2 APOL1 risk alleles versus 384 women with 0/1 risk allele (median, 24 vs 11mg/g; P30 (95% CI, 1.17-3.44) mg/g after multivariable adjustment. APOL1 genotype showed little association with urine IL-18:Cr ratio, KIM-1:Cr ratio, and NGAL:Cr ratio (estimates of -5% [95% CI, -24% to 18%], -20% [95% CI, -36% to -1%], and 10% [95% CI, -26% to 64%], respectively) or detectable urine A1M (prevalence ratio, 1.13; 95% CI, 0.65-1.97) in adjusted analyses. Compared with women with 0/1 allele, women with 2 risk alleles had faster eGFR decline, by 1.2 (95% CI, 0.2 to 2.2) mL/min/1.73m(2) per year, and 1.7- and 3.4-fold greater rates of incident chronic kidney disease (95% CI, 1.1 to 2.5) and 10% annual eGFR decline (95% CI, 1.7 to 6.7), respectively, with minimal attenuation after adjustment for glomerular and tubular injury biomarker levels.LimitationsResults may not be generalizable to men.ConclusionsAmong HIV-infected African American women, APOL1-associated kidney injury appears to localize to the glomerulus, rather than the tubules.

BackgroundExisting data suggest that human immunodeficiency virus (HIV)-infected African Americans carrying 2 copies of the APOL1 risk alleles have greater risk of kidney disease than noncarriers. We sought to determine whether HIV RNA suppression mitigates APOL1-related kidney function decline among African Americans enrolled in the Multicenter AIDS Cohort Study.MethodsWe genotyped HIV-infected men for the G1 and G2 risk alleles and ancestry informative markers. Mixed-effects models were used to estimate the annual rate of estimated glomerular filtration rate (eGFR) decline, comparing men carrying 2 (high-risk) vs 0-1 risk allele (low-risk). Effect modification by HIV suppression status (defined as HIV type 1 RNA level 90% of follow-up time) was evaluated using interaction terms and stratified analyses.ResultsOf the 333 African American men included in this study, 54 (16%) carried the APOL1 high-risk genotype. Among HIV-infected men with unsuppressed viral loads, those with the high-risk genotype had a 2.42 mL/minute/1.73 m(2) (95% confidence interval [CI], -3.52 to -1.32) faster annual eGFR decline than men with the low-risk genotype. This association was independent of age, comorbid conditions, baseline eGFR, ancestry, and HIV-related factors. In contrast, the rate of decline was similar by APOL1 genotype among men with sustained viral suppression (-0.16 mL/minute/1.73 m(2)/year; 95% CI, -.59 to .27; P for interaction

BackgroundAbnormalities in mineral homeostasis are ubiquitous in patients on dialysis, and influenced by race. In this study, we determine the race-specific relationship between mineral parameters and mortality in patients initiating hemodialysis.MethodsWe measured the levels of fibroblast growth factor 23 (FGF23) and 25-hydroxyvitamin D (25 D) in 184 African American and 327 non-African American hemodialysis patients who enrolled between 1995 and 1998 in the Choices for Healthy Outcomes in Caring for ESRD Study. Serum calcium, phosphorus, parathyroid hormone (PTH) and total alkaline phosphatase levels were averaged from clinical measurements during the first 4.5 months of dialysis. We evaluated the associated prospective risk of mortality using multivariable Cox proportional hazards models stratified by race.ResultsPTH and total alkaline phosphatase levels were higher, whereas calcium, phosphorus, FGF23 and 25 D levels were lower in African Americans compared to those of non-African Americans. Higher serum phosphorus and FGF23 levels were associated with greater mortality risk overall; however, phosphorus was only associated with risk among African Americans (HR 5.38, 95% CI 2.14-13.55 for quartile 4 vs. 1), but not among non-African Americans (p-interaction = 0.04). FGF23 was associated with mortality in both groups, but more strongly in African Americans (HR 3.91, 95% CI 1.74-8.82 for quartiles 4 vs. 1; p-interaction = 0.09). Serum calcium, PTH, and 25 D levels were not consistently associated with mortality. The lowest and highest quartiles of total alkaline phosphatase were associated with higher mortality risk, but this did not differ by race (p-interaction = 0.97).ConclusionsAberrant phosphorus homeostasis, reflected by higher phosphorus and FGF23, may be a risk factor for mortality in patients initiating hemodialysis, particularly among African Americans.